The objectives of this grant are to define the immunological events occurring in the course of acute Epstein-Barr virus (EBV) induced infectious mononucleosis (IM). Previous studies have focused on single immunological events (cytotoxic cells, suppressor cells) occurring at one point in time during the course of IM. We will study several immunological events concurrently with sequential studies of individual patients during the acute phase of the disease. The immunological studies will be compared with the virus-host relationship (numbers of EBV-infected cells in the circulation) during the acute phase phase of illness. The focus of these tests will be the analysis of T cell subsets, cytotoxic cells (natural killer (NK), EBV-specific, alloreactive) and suppressor cell activity. Specific populations of T cells will be analyzed by cell separation techniques which isolate activated atypical lymphocytes. Activated T and NK cells will be cloned using a T-cell colony-forming assay in conjunction with long-term T-cell cultures supported by T-cell growth factors. Cloned populations of cells will be analyzed for cell surface markers using monoclonal antibodies and studied in functional cytotoxic, NK, and suppressor cell assays. Finally, the role of interferons (IFN) as immunoregulatory molecules during IM will be explored by quantitation of circulating levels of IFN, assessment of in vitro production of IFN by specific lymphocyte subpopulations and functional studies of the effects of exogenous IFN on cloned T and NK cell populations. Through these studies, we hope to define specific immune mechanisms necessary for the elimination of EBV-infected B lymphocytes which can be evaluated in patients with uncontrolled life-threatening EBV infections. The long-term objective of this study is to arrive at a better understanding of immune system regulation of the EBV-host relationship. This knowledge will be useful in the study of patients with inherited immunological defects which predispose to fatal infections and lymphoproliferative disorders.